Currently available epilepsy drugs only affect the symptoms (seizures), and there is a need for innovative treatments that target the underlying disease. Increasing evidence points to inflammation as a potentially important mechanism in epileptogenesis. In the last decade, a new generation of etiologically realistic syndrome-specific experimental models have been developed which are expected to capture the epileptogenic mechanisms operating in the corresponding patient populations, and to exhibit similar treatment-responsiveness. Recently, an intervention known have broad-ranging anti-inflammatory effects (selective brain cooling) has been found to prevent the development of spontaneously occurring seizures in an etiologically realistic rat model of post-traumatic epilepsy. Several drugs used clinically for other indications also have the potential for inhibiting inflammation, and should be investigated for anti-epileptogenic activity in these models. If results of such studies are positive, these compounds could enter rapidly Phase III trials in patients at high risk of developing epilepsy.